RESEARCH ON MICROBIAL BIOFILMS

RELEASE DATE:  December 20, 2002 

PA NUMBER:  PA-03-047

EXPIRATION DATE:  December 2005, unless reissued. 

National Institute of Dental and Craniofacial Research (NIDCR)
 (http://www.nidcr.nih.gov)
National Institute of Allergy and Infectious Diseases (NIAID)
 (http://www.niaid.nih.gov/)
National Institute on Deafness and Other Communication Disorders (NIDCD) 
 (http://www.nidcd.nih.gov)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 
 (http://www.niams.nih.gov)
National Institute of General Medical Sciences (NIGMS) 
 (http://www.nigms.nih.gov)
National Heart, Lung, and Blood Institute (NHLBI) 
 (http://www.nhlbi.nih.gov)
National Institute of Diabetes and Digestive and Kidney Diseases  (NIDDK) 
 (http://www.niddk.nih.gov/)
National Institute of Biomedical Imaging and Bioengineering (NIBIB) 
 (http://www.nibib.nih.gov) 

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA  

The NIH Institutes listed above invite research grant applications to conduct 
studies on microbial biofilms leading to improved strategies to diagnose, 
prevent and treat biofilm-associated infectious diseases.  Collaborative 
projects, both domestic and international, that bring together investigators 
in diverse scientific disciplines studying biofilms, including microbiology, 
immunology (including mucosal immunology), biochemistry, clinical medicine, 
pathology, bioengineering, material science, imaging technology, and 
mathematical modeling are encouraged.

RESEARCH OBJECTIVES

Background

A biofilm is an accumulation of microorganisms (bacteria, fungi, and/or 
protozoa, with associated bacteriophages and other viruses) embedded in a 
polysaccharide matrix and adherent to solid biologic or non-biologic surface. 
Biofilms are medically important, accounting for over 80 percent of microbial 
infections in the body.  Examples include infections of the:  oral soft 
tissues, teeth and dental implants; middle ear; gastrointestinal tract; 
urogenital tract; airway/lung tissue; eye; urinary tract prostheses; 
peritoneal membrane and peritoneal dialysis catheters, indwelling catheters 
for hemodialysis and for chronic administration of chemotherapeutic agents 
(Hickman catheters); cardiac implants such as pacemakers, prosthetic heart 
valves, ventricular assist devices, and synthetic vascular grafts and stents; 
prostheses, internal fixation devices, percutaneous sutures; and tracheal and 
ventilator tubing.  The microorganisms tend to be far more resistant to 
antimicrobial agents and to be particularly difficult for the host immune 
system to render an appropriate response.

The need for increased research on biofilms is based on many factors:

- Biofilms are remarkably difficult to treat with antimicrobials.  The 
reasons for this are not clear.  Antimicrobials may be readily inactivated or 
fail to penetrate into the biofilm.  In addition, bacteria within biofilms 
have increased (up to 1000-fold higher) resistance to antimicrobial compounds, 
even though these same bacteria are sensitive to these agents if grown under 
planktonic conditions.

- Biofilms increase the opportunity for gene transfer between/among bacteria. 
 This is important since bacteria resistant to antimicrobials or chemical 
biocides can transfer the genes for resistance to neighboring susceptible 
bacteria.  Gene transfer can convert a previous avirulent commensal organism 
into a highly virulent pathogen.

- Certain species of bacteria communicate with each other within the biofilm. 
 As their density increases, the organisms secrete low molecular weight 
molecules that signal when the population has reached a critical threshold.  
This process, called quorum sensing, is responsible for the expression of 
virulence factors.  For example, Pseudomonas aeruginosa produces destructive 
proteinases when the number of these bacteria reach a high enough density in 
the airway biofilms of cystic fibrosis patients.

- Bacteria express new, and sometimes more virulent phenotypes when 
growing within a biofilm.  Such phenotypes may not have been detected in the 
past because the organisms were grown on rich nutrient media under planktonic 
conditions.  The growth conditions are quite different particularly in the 
depths of biofilms, where nutrients and oxygen are usually limited, and waste 
products from neighbors can be toxic.  In short, bacteria found at the bottom 
of the biofilm look and act different than species located at the surface.

- Bacteria embedded within biofilms are resistant to both immunological and 
non- specific defense mechanisms of the body.  Contact with a solid surface 
triggers the expression of a panel of bacterial enzymes, which catalyze the 
formation of sticky polysaccharides that promote colonization and protection.  
The structure of biofilms is such that immune responses may be directed only 
at those antigens found on the outer surface of the biofilm, and antibodies 
and other serum or salivary proteins often fail to penetrate into the biofilm.  
In addition, phagocytes are unable to effectively engulf a bacterium growing 
within a complex polysaccharide matrix attached to a solid surface.  This 
causes the phagocyte to release large amounts of pro-inflammatory enzymes and 
cytokines, leading to inflammation and destruction of nearby tissues.

The field of biofilm research has traditionally been hindered by an inability 
to study the biofilm in non-destructive, three dimensional ways.  In addition, 
it has been difficult or impossible to assess gene expression and metabolism 
of the microbe at the single cell level within a biofilm.  However, as a 
result of advances in laser technology, digital imaging, scanning electron 
microscopy, and new fluorescent probes, researchers can now build a three 
dimensional model of biofilms and identify the location in the biofilm where 
specific genes are being expressed.

This broad-based initiative on microbial biofilms is designed to elucidate 
the mechanisms underlying their formation as well as development of strategies 
for the prevention and treatment of microbial biofilm-associated diseases.  
Moreover, this initiative is intended to capitalize on contemporary research 
in immunology, microbiology, bio-engineering and computer technology that 
might synergize with current biofilm research.

Research Objectives and Scope

Since microbial biofilms are a major problem affecting diverse 
anatomical locations of the body, several components of the NIH have joined in 
this Program Announcement.  Examples of relevant research topics are listed 
below; however the list should not be construed as complete or restrictive.  
Applicants are encouraged to propose other topics that address the overall 
goal of this initiative, which is to advance the understanding of the 
formation of biofilms, the means to control them, and their role in disease.

o  Development of improved imaging of biofilms in situ;

o  Development of improved clinically relevant in vitro and in vivo models 
of biofilms under specific in vivo conditions such as flow rate, nutrient 
content, and temperature;

o  Development of better probes (genetic, metabolic, and immunological) for 
real-time analysis;

o  Development of high throughput methods to identify genes and proteins that 
are differentially expressed in biofilms; 

o  Studies of quorum sensing/signaling molecules;

o  Studies of the exchange of genetic material within biofilms;

o  Studies of organic contaminants on substrata, and their influence on 
biofilm structure;

o  Development of novel approaches to control pathogenic bacteria by, 
for example, devising strategies to favor growth of non-pathogenic 
microorganisms in biofilm communities;

o  Studies of interactions of biofilms with host tissues and artificial 
implants;

o  Development or use of novel agents, materials, or coatings for preventing 
or treating infections related to cardiovascular and pulmonary devices, 
and orthopaedic devices (artificial joints), internal fixation 
devices, percutaneous sutures, and engineered tissues;

o  Studies of pathogenic mechanisms of microbes growing in biofilms;

o  Elucidation of mechanisms of resistance of biofilms to antimicrobial 
agents;

o  Studies of host immune responses, both innate and adaptive to biofilms;

o  Studies of the potential role of biofilms and host response in the 
development of systemic inflammatory response syndrome, septic shock, acute 
respiratory distress syndrome, and multiple organ dysfunction syndrome in 
injured or critically ill patients, or in model systems reflecting these 
clinical conditions;

o  Studies of infectious lung disease in cystic fibrosis;

o  Studies on the potential of diagnostic procedures such as 
bronchoalveolar lavage and bronchoscopy to disturb local biofilm flora and 
inoculate distant locations;

o  Development of mathematical models and computer simulations of biofilms;

o  Development of the methodology for the prevention and control of biofilms 
from catheters, orthopaedic devices and other clinically important solid 
surfaces; and,

o  Sex, gender or age related issues involved in biofilm formation, 
prevention or treatment.

MECHANISM(S) OF SUPPORT 

This PA will use the NIH R01 and R21 award mechanisms.  As an applicant, you 
will be solely responsible for planning, directing, and executing the 
proposed project.  

The R21 proposals should have the potential for truly groundbreaking impact.  
Use of this mechanism to explore new biomedical approaches to address basic 
and applied research questions is encouraged. Applicants are encouraged to 
contact program staff for advice about choosing the appropriate grant 
mechanism. R21 applications may request up to a total of two years of 
support, and total direct costs for the two years cannot exceed $275,000.      

The objective of the R21 mechanism is to support innovative, high risk/high 
impact research requiring preliminary testing or development; exploration of 
the use of approaches and concepts new to biofilm research; research and 
development of new technologies, techniques or methods; or initial research 
and development of data upon which significant future research may be built.  
Applications will be considered as high impact if they demonstrate the 
potential for ground-breaking, precedent-setting significance, and high risk 
because they either lack sufficient preliminary data to ensure their 
feasibility, or involve using a new model system or technique. While this PA 
is intended to encourage innovation and high impact research, and while 
minimal preliminary data are expected to be described in the application, 
applications should clearly indicate that the proposed research and/or 
development is scientifically sound, that the qualifications of the 
investigators are appropriate, and that resources available to the 
investigators are adequate.  

This PA uses just-in-time concepts.  It also uses the modular as well as the 
non-modular budgeting formats
(see http://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, if you are submitting an application with direct costs in each
year of $250,000 or less, use the modular format.  Otherwise follow the
instructions for non-modular research grant applications.

ELIGIBLE INSTITUTIONS 

You may submit (an) application(s) if your institution has any of the 
following characteristics:

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign
o Faith-based or community-based organizations 

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.   

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity to 
answer questions from potential applicants. Inquiries may fall into two 
areas:  scientific/research and financial or grants management issues:

o Direct your questions about scientific/research issues to:

Dennis F. Mangan, Ph.D.
Division Basic and Translational Sciences
National Institute of Dental and Craniofacial Research
Building 45, Suite 18
Bethesda, MD  20892-6402
Telephone:  (301) 594-2421
FAX:  (301) 402-8318
Email:  Dennis.Mangan@nih.gov

Peter Moy, Ph.D.
National Institute of Biomedical Imaging and Bioengineering
Democracy Two, Suite 200 MSC 5469
6707 Democracy Boulevard
Bethesda, MD 20892-5469
Telephone: (301) 496-9270
FAX: (301) 480-0679
Email: moype@mail.nih.gov

Lawrence Agodoa, M.D.
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS13B, MSC 6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-7717
FAX:  (301) 480-3510
Email:  AgodoaL@extra.niddk.nih.gov

Martha S. Lundberg, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 9146
Bethesda, MD  20892-7940
Telephone:  (301) 435-1802
FAX:  (301) 480-1335
Email:  lundberm@nhlbi.nih.gov

Nancy L. Freeman, Ph.D.  
National Institute on Deafness and Other Communication Disorders  
Executive Plaza South-400C  
6120 Executive Blvd. MSC-7180  
Bethesda, MD 20892-7180  
Telephone: (301) 402-3458  
FAX: (301) 402-6251
Email:  nancy_freeman@NIH.gov  

Christopher E. Taylor, Sc.D.
Division of Microbiology & Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 3128, MSC-7630
6700-B Rockledge Drive
Bethesda, MD 20892-7630
Telephone: (301) 496-5305
FAX: (301) 496-8030
Email: ct18m@nih.gov

James S. Panagis, MD, MPH
Musculoskeletal Diseases Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH
One Democracy Plaza
6701 Democracy Boulevard, Suite 800
MSC 4872
Bethesda, MD 20892-4872
Telephone:  (301) 594-5055
FAX:   (301) 480-4543
Email:   jp149d@nih.gov

Scott Somers, Ph.D. 
National Institute of General Medical Sciences
Building 45; Room 2AS-49
Bethesda, MD 20892
Telephone:  (301) 594-5560
FAX:  (301) 480-2802
Email:  somerss@nigms.nih.gov

o Direct your questions about financial or grants management matters to:

Mary Daley
Chief Grants Management Officer
National Institute of Dental and Craniofacial Research
45 Center Drive MSC 6402
Bldg. 45, Rm. 4AN44B
Bethesda, MD  20892-6402
Telephone: (301) 594-4808
FAX: (301) 480-8303
Email: md74u@nih.gov

Nancy Curling
National Institute of Biomedical Imaging and Bioengineering
Democracy Two, Suite 900
6707 Democracy Boulevard
Bethesda, MD 20892
Telephone: (301) 496-9315
FAX: (301) 480-4974
Email: curlingn@mail.nih.gov

Trude Hilliard
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases
2 Democracy, Room 717
6707 Democracy Boulevard
Bethesda, MD 20892-5456
Telephone: (301) 594-8859
FAX: (301) 480-4237
Email:  HillardT@extra.niddk.nih.gov.

Edward E. McGeehan
Grants Operation Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Rm 7142
Bethesda, MD  20892-7926
Telephone: (301) 435-0148
FAX:  (301) 480-0422
Email: mcgeehae@nhlbi.nih.gov

Sara Stone 
Chief, Grants Management Branch 
Division of Extramural Research
National Institutes of Health
National Institute on Deafness and Other Communication Disorders
Executive Plaza South-400C
6120 Executive Blvd.  MSC-7180
Bethesda, MD  20892-7180 
Telephone:  (301) 402-0909 
FAX:  (301) 402-1758 
Email:  stones@nidcd.nih.gov

Mollie Shea  
Division of Extramural Activities   
National Institute of Allergy and Infectious Diseases   
Room 2262, MSC-7614  
6700-B Rockledge Drive   
Bethesda, MD  20892-7614   
Telephone:  (301) 402-6576 
FAX:  (301) 480-3780
Email: ms256g@nih.gov

Melinda B. Nelson
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institutes of Health
One Democracy Plaza
6701 Democracy Boulevard, Suite 800
MSC 4872
Bethesda, Maryland  20892
Telephone:  (301) 594-3535
FAX:  (301) 480-5450
Email:  MN23Z@NIH.GOV

Ms. Toni Holland
Grants Management Office
National Institute of General Medical Sciences
45 Center Drive, Room 2AN-50B, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-5132
FAX:  (301) 480-2554
Email:  hollanda@nigms.nih.gov

Since Institute staff assignments may change during the course of this 
announcement, applicants should check the following website for the most 
recent contact information:  
http://www.nidcr.nih.gov/funding/contacts_PA_Biofilms2003.asp.  

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov.

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which 
are available at http://grants.nih.gov/grants/dates.htm.  Application 
deadlines are also indicated in the PHS 398 application kit.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS:   Applications 
requesting up to $250,000 per year in direct costs must be submitted in a 
modular grant format.  The modular grant format simplifies the preparation of 
the budget in these applications by limiting the level of budgetary detail.  
Applicants request direct costs in $25,000 modules.  Section C of the 
research grant application instructions for the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

SUPPLEMENTAL INSTRUCTIONS: 

R21 Applications:  All application instructions outlined in the PHS 398 
application kit are to be followed with the following modifications for R21 
applications:

1. FACE PAGE, Item 6:  Up to a total of two years of support may be 
requested.  Total direct costs for the two years cannot exceed $275,000.  

2. Items a-d of the Research Plan for the R21 application may not exceed 
fifteen (15) pages, including tables and figures.  The following information 
should be taken into account for items a, b and c:  

o  Item a, SPECIFIC AIMS--The instructions for this section suggest that the 
applicant state "the hypotheses to be tested".  Since some applications 
submitted in response to this PA may also be design- or problem-driven (e.g., 
development of novel technologies), or need-driven (initial research to 
develop a body of data upon which future research will build), hypothesis 
testing per se may not be the driving force in developing such a proposal 
and, therefore, may not be applicable.  The application should state the 
hypotheses, design, problem and/or need which will drive the proposed 
research.

o  Item b, BACKGROUND AND SIGNIFICANCE--In this section, it is important to 
identify clearly how the application addresses the specific objectives of 
this PA and the purpose of the R21 mechanism.

o  Item c, PRELIMINARY STUDIES/PROGRESS REPORT—No preliminary data are 
required for an R21 application.  

3. APPENDIX -  Up to five articles can be submitted in the appendix. 

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR:   
Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of the NIH 
institutes or centers (IC) who has agreed to accept assignment of the 
application.   

Applicants requesting $500,000 or more must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the 
application, i.e., as you are developing plans for the study; 

2) Obtain written agreement from the IC staff that the IC will accept your 
application for consideration for award; and,
  
3) Identify, in a cover letter sent with the application, the staff member 
and IC who agreed to accept assignment of the application.  

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised 
version of these grant application types. Additional information on this 
policy is available in the NIH Guide for Grants and Contracts, October 19, 
2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html. 

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and five signed photocopies in one 
package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING: Applications must be received by or mailed on or 
before the receipt dates described at 
http://grants.nih.gov/grants/funding/submissionschedule.htm.  The CSR will 
not accept any application in response to this PA that is essentially the 
same as one currently pending initial review unless the applicant withdraws 
the pending application.  The CSR will not accept any application that is 
essentially the same as one already reviewed.  This does not preclude the 
submission of a substantial revision of an application already reviewed, but 
such application must include an Introduction addressing the previous 
critique.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review group 
convened in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o Receive a written critique
o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a second level review by the appropriate national advisory council 
or board.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to discuss the following 
aspects of your application in order to judge the likelihood that the 
proposed research will have a substantial impact on the pursuit of these 
goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these criteria 
in assigning your application's overall score, weighting them as appropriate 
for each application.  Your application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score.  For example, you may propose to carry out 
important work that by its nature is not innovative but is essential to move 
a field forward.

(1) SIGNIFICANCE:  Does your study address an important problem? If the aims 
of your application are achieved, how do they advance scientific knowledge?  
What will be the effect of these studies on the concepts or methods that 
drive this field?

(2) APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Do you acknowledge potential problem areas and consider alternative 
tactics?

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your project challenge 
existing paradigms or develop new methodologies or technologies?

(4) INVESTIGATOR: Are you appropriately trained and well suited to carry out 
this work?  Is the work proposed appropriate to your experience level as the 
principal investigator and to that of other researchers (if any)?

(5) ENVIRONMENT:  Does the scientific environment in which your work will be 
done contribute to the probability of success?  Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements?  Is there evidence of institutional 
support?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your 
application will also be reviewed with respect to the following:

PROTECTIONS:  The adequacy of the proposed protection for humans, animals, or 
the environment, to the extent they may be adversely affected by the project 
proposed in the application.

INCLUSION:  The adequacy of plans to include subjects from both genders, all 
racial and ethnic groups (and subgroups), and children as appropriate for the 
scientific goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria included in the 
section on Federal Citations, below)

BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds 
with all other recommended applications.  The following will be considered in 
making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities

REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD:  Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of the 
research. This policy results from the NIH Revitalization Act of 1993 (Section 
492B of Public Law 103-43).

All investigators proposing clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm. 

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on 
hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm and at  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide the official NIH 
identifier(s)for the hESC line(s)to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.   Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of "Healthy 
People 2010," a PHS-led national activity for setting priority areas. This PA 
is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal 
Domestic Assistance Numbers 93.121 (NIDCR), 93.856 (NIAID), 93.173 (NIDCD), 
93.846 (NIAMS), 93.859 (NIGMS), 93.837 (NHLBI), 93.849 (NIDDK), 93.286 and 
93.287 (NIBIB) and is not subject to the intergovernmental review requirements 
of Executive Order 12372 or Health Systems Agency review.  Awards are made 
under authorization of Sections 301 and 405 of the Public Health Service Act 
as amended (42 USC 241 and 284) and administered under NIH grants policies 
described at http://grants.nih.gov/grants/policy/policy.htm and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.


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